WEEK 4 ANTIFUNGAL AND TDM

Which are the antifungal agents below require TDM for dose-response optimization ( more than one answer) 

• fluconazole

• isavuconazole

• micafungin

• voriconazole

• itraconazole

A 20 years old male. Mr Papaya with AML in neutropenic sepsis, started on IV voriconazole.  Serum galactomannan was a positive and  air-crescent sign seen in CT thorax. Body weight is 50kg. What is the appropriate dose of IV voriconazole ? Creatinine was 200  uml/L

• 300 mg 12 hourly on day 1. Then 200 mg 12 hourly

• in view of renal impairment, 150 mg 12 hourly on day 1. Then, 100 mg 12 hourly

• 200 mg 12 hourly

• voriconazole is contraindicated

• 300 mg 12 hourly, check TDM and adjust the dose accordingly

  When blood specimens for Voriconazole TDM should be collected? 

 

• Immediately after the loading dose

• On day 5 of therapy

• On day 7 of therapy 

• TDM is not required as drug-drug interaction not suspected

• On day 14 of therapy 

Mr Papaya had episodes of seizures secondary to CNS leukemia. He was started on IV phenytoin. The  serum Voriconazole levels ( 1 week apart) were 3.5mg/L and 2.8 mg/L while on 200mg BD, prior to the incidence of seizure. He is on Oral voriconazole 200 mg BD but had break through fever and serum GM increased from 0.8 to 1.5. What would you do now ?

    

• Increase Oral voriconazole to 250mg BD

• Convert to IV voriconazole 200 mg BD for better bioavailability 

• Withhold phenytoin 

• Check Voriconazole TDM and adjust the dose accordingly  

 Mr Papaya ‘s serum voriconazole was 0.7mg/L, he mentioned he had 2 days of diarrhea, with suspected break through aspergillosis . What could have possibly happened ?

• Non-complaint to Oral voriconazole , or missed dose

• Poor absorption of oral voriconazole  

• Drug-drug interaction

• Sampling error  

• All the above 

Following Q5,  What would you do now ?

• Cease oral voriconazole, switch to IV amphotericin B  

• Convert to IV voriconazole, increase dose to 250 mg 12 hourly and repeat the serum level 

• Cease oral voriconazole, switch to Posaconazole

• Cease oral voriconazole, switch to Anidulafungin 

• Do nothing  

Drugs that require TDM monitoring have  pharmacological characteristics as below  (more than one answer):

• Nonlinear pharmacokinetics

   

• Poor bioavailability

• Inter and intra-patient variability pharmacokinetics 

• Drugs affected by genetic polymorphism

• All drugs need TDM 

Which of the following require(s)  serum level monitoring ?

• Deoxycholate amphotericin B

• Liposomal amphotericin B 

• Micafungin 

• Caspofungin

• Flucytosine

Methods of determining serum drug concentration include ? ( more than one answer)

• POCT

• Bioassay

• Liquid Chromatography with mass spectrometry   

• PCR 

• HPLC

Ideally TDM service should involve (more than one answer) :

• Pharmacists 

• Laboratory personnel /expert

• Clinicians

• IT personnel

• all the above